Lysine acetylation is a major post-translational modification in histones and other proteins that is catalysed by the ‘writer’ lysine acetyltransferases (KATs) and mediates interactions with bromodomains (BrDs) and other ‘reader’ proteins. KATs and BrDs play key roles in regulating gene expression, cell growth, chromatin structure, and epigenetics and are often dysregulated in disease states, including cancer. There have been accelerating efforts to identify potent and selective small molecules that can target individual KATs and BrDs with the goal of developing new therapeutics, and some of these agents are in clinical trials. Here, we summarize the different families of KATs and BrDs, discuss their functions and structures, and highlight key advances in the design and development of chemical agents that show promise in blocking the action of these chromatin proteins for disease treatment.

赖氨酸乙酰化是组蛋白和其他蛋白质中的主要翻译后修饰，由“写入者”赖氨酸乙酰转移酶 （KAT） 催化，并介导与溴结构域 （BrD） 和其他“读取者”蛋白的相互作用。KAT 和 BrD 在调节基因表达、细胞生长、染色质结构和表观遗传学方面起关键作用，并且在疾病状态（包括癌症）中经常失调。为了开发新的疗法，人们一直在加速寻找可以靶向单个 KAT 和 BrD 的强效和选择性小分子，其中一些药物正处于临床试验阶段。在这里，我们总结了 KAT 和 BrD 的不同家族，讨论了它们的功能和结构，并强调了化学试剂的设计和开发的关键进展，这些化学试剂有望阻断这些染色质蛋白在疾病治疗中的作用。